Life after total skin electron irradiation; A perspective through the eyes of a radiation oncologist.

Mycosis fungoides (MF) remains a challenge as a disease from its diagnosis through treatment and follow-up. The rarity of the disease and uncharacteristic clinical manifestations pose difficulty in diagnosis, and the lack of treatment facilities adds to the management woes. Though the Stanford technique is the most accepted modality of total skin electron beam therapy (TSEBT), the implementation details are still unstandardized. Different centers adopt different methodologies as per their convenience and suitability. We present a patient of MF with many dimensions of prediagnosis clinical features to the diagnosis, treatment, and follow-up with subsequent developments over a period of 24 years that may help to understand the disease and management in a better manner.

Metronomic Therapy in Palliation of Oral Cancer Patients-A Home Based Approach at the End of Life.

INTRODUCTION: Despite the development of targeted therapies for the management of oral cancer patients, the cost of treatment is a concern in middle- and low-income countries. The present study assessed the feasibility of low-cost metronomic therapy as an alternative treatment modality in patients with unresectable or inoperable oral cancers. METHODOLOGY: The study was a prospective, single-arm study. Unresectable, inoperable, and metastatic lip and oral cavity cancers were started on metronomic therapy, a combination of oral methotrexate 15 mg/m2 once a week and oral celecoxib 200 mg twice daily, as palliative therapy. The primary endpoint was overall survival. The secondary endpoints were a response to metronomic therapy, compliance, and toxicity. RESULTS: From June 2018 to May 2020, 25 patients were started on metronomic therapy. The median age was 60 years. The median overall survival was 8.8 months. At eight weeks of therapy, 11 patients (44%) had a partial response, ten patients had stable disease (40%), and four patients had progressive disease (16%). The compliance with the therapy was 100%, and one patient (4%) developed grade III toxicity. CONCLUSIONS: Considering the resource constraints and cost limitations in low and middle-income countries, oral metronomic therapy in the form of methotrexate and celecoxib should be regarded as a suitable regimen in the palliative treatment of patients with unresectable, metastatic, or advanced, recurrent cancers.

EZH2 knockdown in tamoxifen-resistant MCF-7 cells unravels novel targets for regaining sensitivity towards tamoxifen.

BACKGROUND: Acquired resistance to drug involves multilayered genetic and epigenetic regulation. Inhibition of EZH2 has proven to reverse the tamoxifen resistance back to the sensitive state in breast cancer. However, the molecular players involved in EZH2-mediated effects on tamoxifen-resistant MCF-7 cells are unknown. This study was conducted to understand the global change in proteome profile of tamoxifen-resistant MCF-7 breast cancer cells upon EZH2 knockdown. METHODS: Tamoxifen resistance MCF-7 breast cancer cells were established using increasing concentrations of 4-hydroxy tamoxifen. Using label free proteomics approach, we studied the alteration in total proteome in resistant cells as well as cells transfected with siEZH2 in comparison to sensitive and cells transfected with non-targeting siRNA. RESULTS: Here, we report list of proteins that were previously not recognized for their role in tamoxifen resistance and hold a close association with breast cancer patient survival. Proteins Annexin A2, CD44, nucleosome assembly protein 1, and lamin A/C were among the most upregulated protein in tamoxifen-resistant cells that were found to be abrogated upon EZH2 knockdown. The study suggests the involvement for various proteins in acquiring resistance towards tamoxifen and anticipates further research for investigating their therapeutic potentials. CONCLUSION: Overall, we propose that targeting EZH2 or the molecules down the cascade might be helpful in reacquiring sensitivity to tamoxifen in breast cancer.

A nationally representative case-control study of smoking and death in India.

BACKGROUND: The nationwide effects of smoking on mortality in India have not been assessed reliably. METHODS: In a nationally representative sample of 1.1 million homes, we compared the prevalence of smoking among 33,000 deceased women and 41,000 deceased men (case subjects) with the prevalence of smoking among 35,000 living women and 43,000 living men (unmatched control subjects). Mortality risk ratios comparing smokers with nonsmokers were adjusted for age, educational level, and use of alcohol. RESULTS: About 5% of female control subjects and 37% of male control subjects between the ages of 30 and 69 years were smokers. In this age group, smoking was associated with an increased risk of death from any medical cause among both women (risk ratio, 2.0; 99% confidence interval [CI], 1.8 to 2.3) and men (risk ratio, 1.7; 99% CI, 1.6 to 1.8). Daily smoking of even a small amount of tobacco was associated with increased mortality. Excess deaths among smokers, as compared with nonsmokers, were chiefly from tuberculosis among both women (risk ratio, 3.0; 99% CI, 2.4 to 3.9) and men (risk ratio, 2.3; 99% CI, 2.1 to 2.6) and from respiratory, vascular, or neoplastic disease. Smoking was associated with a reduction in median survival of 8 years for women (99% CI, 5 to 11) and 6 years for men (99% CI, 5 to 7). If these associations are mainly causal, smoking in persons between the ages of 30 and 69 years is responsible for about 1 in 20 deaths of women and 1 in 5 deaths of men. In 2010, smoking will cause about 930,000 adult deaths in India; of the dead, about 70% (90,000 women and 580,000 men) will be between the ages of 30 and 69 years. Because of population growth, the absolute number of deaths in this age group is rising by about 3% per year. CONCLUSIONS: Smoking causes a large and growing number of premature deaths in India.

Total skin electron irradiation therapy in mycosis fungoides using high-dose rate mode: a preliminary experience.

INTRODUCTION: Total skin electron irradiation (TSEI) therapy is the treatment of choice for mycosis fungoides. However, conventional TSEI therapy is time consuming as well as patient unfriendly. Therefore we used high-dose rate (HDR) mode TSEI in these patients. High-dose rate mode of TSEI is a technological innovation attached to a Linear Accelerator (Philips, SL-20, Netherlands), which can deliver an electron beam of 30 Gy/min at the iso-center. The iso-center faces the patient, 100 cm away from the target of the linear accelerator. The patient is treated at a distance of 10 feet from the iso-center of the linear accelerator. The dose delivered to the skin was 1.13 Gy/min, making the treatment execution much easier and patient compliance much better. METHODS: Seven male patients between 40 and 64 years in age having mycosis fungoides for 9-18 months were treated by TSEI using high-dose rate mode between 1998 and 2000. The TSEI was performed according to the Stanford technique, delivering a total dose of 36 Gy. Each patient received a dose of 1.2 Gy/field/day. There were six fields, i.e. anterior, posterior, left and right anterior obliques, and left and right posterior obliques in both the upper and lower parts of the body. The eyes and nails were shielded at each session of radiotherapy. The times taken at each session of the therapy and radiation-associated side-effects were determined in each patient. The patients were followed up to 26 months (median 9 months) to look for any relapse. RESULTS: Three patients had early stage disease (IB) whereas four patients had advanced disease (IIB). Six patients out of these had complete remission following TSEI while one patient died as a result of progression of the disease during treatment. The treatment time taken at each treatment session in each individual patient was approximately 15 min. Radiation-associated morbidity was seen in all patients. Cutaneous lesions relapsed in two patients after 4 and 10 months, respectively, while four patients were alive without the disease at the end of 2 years. CONCLUSIONS: Total skin electron irradiation using high-dose rate mode delivery of electrons is an easy, better, compliant and effective therapeutic modality for treatment of mycosis fungoides with an acceptable range of toxicities.

An unusual presentation of a malignant jejunal tumor and a different management strategy.

BACKGROUND: Malignant small bowel tumors are very rare and leiomyosarcoma accounts for less than 15% of the cases. Management of these tumors is challenging in view of nonspecific symptoms, unusual presentation and high incidence of metastasis. In this case report, an unusual presentation of jejunal sarcoma and management of liver metastasis with radiofrequency ablation (RFA) is discussed. CASE PRESENTATION: A 45-year-old male presented with anemia and features of small bowel obstruction. Operative findings revealed a mass lesion in jejunum with intussusception of proximal loop. Resection of bowel mass was performed. Histopathological findings were suggestive of leiomyosarcoma. After 3-years of follow-up, the patient developed recurrence in infracolic omentum and a liver metastasis. The omental mass was resected and liver lesion was managed with radiofrequency ablation. CONCLUSION: Jejunal leiomyosarcoma is a rare variety of malignant small bowel tumor and a clinical presentation with intussusception is unusual. We suggest that an aggressive management approach using a combination of surgery and a newer technique like RFA can be attempted in patients with limited metastatic spread to liver to prolong the long-term survival in a subset of patients.